title: Renal response to infusion of dopamine precursors in anaesthetized rats.
abstract: In the present study the renal response to intravenous infusion of the catecholamine precursors L-dihydroxyphenylalanine (L-DOPA) or L-tyrosine was investigated in thiopentone sodium-anaesthetized Sprague-Dawley rats. Glomerular filtration rate (GFR) was assessed by renal clearance of inulin, urinary concentration of dopamine (U(DA)V) by HPLC and sodium excretion (U(Na)V) by flame photometry. We found that basal U(DA)V was 6.5 +/- 0.5 pmol/min per 100 g body weight (mean +/- SEM). Intravenous infusion of L-tyrosine at 0. 1-3.0 micromol/min dose dependently enhanced U(DA)V (17 +/- 3 to 144 +/- 14 pmol/min respectively) with higher doses of L-tyrosine resulting in no further increase in U(DA)V. Compared with L-tyrosine administration significantly lower doses of L-DOPA (0.07 to 35 nmol/min) caused increases in U(DA)V which were orders of magnitude higher (18 +/- 1 to 7800 +/- 470 pmol/min, respectively) and did not show saturation characteristics. GFR did not change in response to L-tyrosine or L-DOPA infusion. No variations in urinary flow rate or in U(Na)V could be observed which were significantly correlated to changes in U(DA)V. In contrast, intravenous infusion of dopamine at a dose of 6 nmol/min significantly increased GFR by 35 +/- 6.2% and urinary flow rate by over 2-fold. Immunohistochemistry with light microscopy revealed no tyrosine hydroxylase in the kidney. Therefore, dopamine synthesis in the tubular cells mainly depends on the renal supply of L-DOPA. The unchanged GFR and U(Na)V in spite of large variations of U(DA)V argue against the hypothesis that intratubular dopamine plays a functional role in the regulation of hemodynamics or sodium transport in the kidney. Renal dopamine excretion may rather represent an effective pathway for the elimination of catecholamine precursors from the plasma.
authors.affiliation: Pharmakologisches Institut der Universität Tübingen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Mühlbauer
authors.forename: C H
authors.initials: CH
authors.lastname: Gleiter
authors.forename: C
authors.initials: C
authors.lastname: Gies
authors.forename: G
authors.initials: G
authors.lastname: Luippold
authors.forename: P A
authors.initials: PA
authors.lastname: Löschmann
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology / Q000652:urine; D005919:Glomerular Filtration Rate; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D014443:Tyrosine; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine